Project #3 of this program project will focus on clinical trials of dendritic cell (D) immunotherapy in the post-high dose chemotherapy setting. This proposal is based upon the premise that a clinically effective cell- mediated immune response against human tumors can be elicited by activation of tumor antigen-specific T lymphocytes. To overcome deficiencies in in vivo antigen presentation, we propose an immunotherapy strategy using specialized antigen presenting cells, DC, generated and loaded ex vivo with RNA encoding a tumor associated antigen, carcinoembryonic antigen (CEA). We are currently conducting a phase I clinical trial of active immunotherapy in patients with CEA over- expressing metastatic cancer who will receive intravenous infusions of CEA RNA-transfected DC. Preliminary results demonstrate the generation of CEA-specific T cells in 6 out of 10 patients with advanced metastatic disease following immunotherapy. It is hypothesized that the generation of CEA-specific CTL after CEA RNA DC infusion will occur in a greater percentage of patients and achieve clinically relevant levels in patients with minimal residual disease. Because CEA is over-expressed in 50% of breast cancers, one setting which we can test this hypothesis is in patients with metastatic breast cancer who have achieved a partial of complete clinical response following high dose chemotherapy (HDC) and autologous peripheral blood progenitor cell transplant (ABPCT) at risk of disease progression or relapse. We propose an immunologic phase II clinical trial of active immunotherapy with CEA RNA transfected DC to be initiated 2 months following ABPCT. This clinical study is designed to determine the immunologic response of post-transplant active immunotherapy, by determining the magnitude of a CEA-specific cellular immune response following immunization. We propose to correlate immunologic response to CEA with functional reconstitution of T cell immunity. The overall goal of this project is to determine the immunologic response of active immunotherapy post-transplant as a prelude to performing subsequent clinical efficacy trials of post- transplantation active immunotherapy.